The role of the creatine kinase system in maintaining neuronal function is being studied in the hippocampus. Antibody to the BB isozyme of creatine kinase is applied to control and post-ischemic gerbil brains to determine if a loss in neuronal content of this enzyme leads to the death of CA1 pyramidal cells at 3-4 days post-ischemia. At the light microscope level there has been no observable deficit prior to neuronal degeneration. Loss of the CA1 cells did result in marked loss of antibody labeling in the CA1 region of the anterior hippocampus. These observations are being extended to the electron microscope level. The staining pattern may indicate areas of high energy demand which would be expected to show the greatest sensitivity to ischemia or anoxia. A comparison is being made of the rates of change in high energy phosphate (ATP and PCr) concentrations during anoxia and ischemia in vitro. The results should indicate the relative importance of anaerobic glycolysis in maintaining synaptic transmission during anoxia in the hippocampal slice. While ischemia appears to cause a more rapid fall in slice ATP levels, it is not clear that the evoked electrophysiological response is abolished more rapidly under the conditions compared to anoxia. Several electrophysiological parameters are being studied in hippocampal slices prepared from gerbils before or for 4 days following 5 min. bilateral ischemia. The results fail to show any significant difference between CA1 cells in the anterior hippocampus, which die within 4 days, and those which survive in the lateral hippocampus.